The present invention relates to the field of cancer diagnosis and treatment, and more particularly to methods of detecting and treating carcinoma that elicit carcinoembryonic antigen (CEA). In particular, this invention relates to the identification of new cancer markers, CEA binding proteins, and methods of isolating such CEA-binding proteins, antibodies specific for these proteins, as well as methods useful in the diagnosis, detection, and monitoring of carcinoma.
Colorectal carcinoma is a cancer which affects approximately 600,000 additional people worldwide per year. The prognosis is poor in about 50% of the cases because the tumor is often not detected until the disease has spread and has reached a terminal stage. Early diagnosis is important to increase chances of arresting the carcinoma before it metastasizes, thereby leading to an improved prognosis.
A widely used method of the identification of cancerous tissue is to determine its structural resemblance to fetal or immature tissue. In this way, tumors can be classified depending on the degree of cellular differentiation; they can be undifferentiated, poorly differentiated, moderately differentiated or well differentiated. In addition, the behavior of a given tumor can often be related to its degree of differentiation. For example, poorly differentiated tumors tend to grow more rapidly and metastasize earlier than do differentiated tumors which more closely resemble the tissue of origin. Poorly differentiated tumors tend to have a poor prognosis and are difficult to detect.
One method of early tumor diagnosis is detection of the presence of a marker or antigen specific for a particular tumor. These normally proteinaceous markers are synthesized by the tumor, and may be found in the serum and/or on the surface of the tumor. Only a limited number of tumor markers for colorectal carcinoma have thus far been found to have clinical use. These include CEA and the sialyated Lewis a antigen (CA 19.9). Unfortunately, approximately 40% of patients whose condition has been accurately diagnosed as colorectal carcinoma do not have elevated plasma levels of either of these antigens when initially examined. In the case of CEA, this may be because this antigen is so rapidly cleared from the circulation. Recently, however, two new cancer markers, the carcinoma orosomucoi-related antigen (CORA) (U.S. Pat. No. 4,914,021) and the and the CC-glycoprotein (U.S. Pat. No. 4,921,789) have been discovered by applicants. However, there is no commercially available serodiagnostic marker which can be used to detect the tumor and to monitor therapy for this group.
Production of some tumor markers e.g., CEA and CA 19.9, by tumor cells in vitro correlates with a greater degree of cellular differentiation. For example, CEA and CA 19.9 are present to a far lesser degree on poorly differentiated or undifferentiated cancer cells than on those which are more differentiated. Accordingly, many patients with undifferentiated colorectal carcinomas never develop elevated serum levels of either of these markers, even in the terminal stages of the cancer. There is also considerable overlap between the presence of CA 19.9 and CEA, the patient with a normal CEA level and an elevated level of CA 19.9 being the exception rather than the rule. Therefore, new markers suitable for identifying and monitoring undifferentiated tumors would be of great value.
Accordingly, it is an object of this invention to provide new markers for the detection of carcinoma.
It is another object of the invention to provide new markers suitable for diagnosing and monitoring, and treatment of carcinoma.
Yet another object is to provide antibodies specific for these new markers.
Still another object is to provide a method of isolating CEA-binding proteins that eliminates contamination by CEA.
A further object of the present invention is to provide a method and kit for the detection and monitoring of carcinoma in patients using antibodies specific for markers on carcinoma cells.
Yet another object of the invention is to provide a hybridoma which produces a monoclonal antibody that recognizes both undifferentiated and poorly differentiated carcinoma cells.
A still further object is to provide screening procedures for detecting the presence of carcinoma cells at all stages of differentiation.
These and other objects of the invention will be apparent from the description, drawing and claims which follow.